Objective To explore function-structure covariant patterns in Alzheimer's disease(AD)and mild cognitive impairment(MCI),and to investigate their associations with cognitive function and activities of daily living.Methods three-way parallel group independent component analysis(three-way pGICA),was used to identify the covariant patterns of resting-state functional MRI temporal data,gray matter density maps,and fractional anisotropy(FA)maps,and the differences between different groups were compared.Furthermore,the associations of covariant patterns with the Montreal Cognitive Assessment-Basic(MoCA_B)Scale scores and Activities of Daily Living Scale scores were analyzed.Results The function-structure covariant patterns in AD and MCI were characterized by the enhanced negative functional connectivity between the left posterior salience network and the right default mode network,the decreased gray matter density in the bilateral dorsolateral prefrontal cortex,and the reduced FA values in the left superior corona radiata(correlations:P<0.001,FDR corrected).Compared with HC group,AD group showed significant abnormalities in all identified covariant patterns(P<0.01,FDR corrected),but MCI group only exhibited a significant decrease in gray matter density in the bilateral dorsolateral prefrontal cortex(P<0.05,FDR corrected).Additionally,AD group had significantly lower FA value in the left superior corona radiata than MCI group(P<0.05,FDR corrected).The loadings reflecting the degree of covariation were significantly correlated with the Activities of Daily Living Scale scores(P<0.05,FDR corrected)but not with MoCA_B Scale scores.Conclusion The function-structure covariant patterns in AD and MCI are consistent with the declines in activities of daily living.The multimodal fusion analysis(three-way pGICA)provides a novel approach to understand the brain damage mechanisms underlying the covariant evolution of MCI and AD.

Objective To investigate alterations in interhemispheric functional connectivity(FC)in the cerebral cortices connected via the corpus callosum in patients with Alzheimer's disease(AD),and to explore their relationships with cognitive function and activities of daily living.Methods Resting-state functional magnetic resonance imaging data were collected from 28 patients with Alzheimer's dementia(d-AD),47 patients with mild cognitive impairment(MCI),and 37 healthy controls(HC).Using a trancallosal tract template,32 pairs of homologous cortical brain regions directly connected to 32 subregions of the corpus callosum were selected as regions of interest for interhemispheric FC analysis.Further correlation analyses were performed between FC values in patient groups and their scores on the Montreal Cognitive Assessment-Basic(MoCA-B)Scale and the Activities of Daily Living(ADL)Scale.Results Compared with HC group,both MCI and d-AD groups exhibited hyperconnectivity(significantly increased FC)in interhemispheric non-homologous brain regions.Specifically,hyperconnectivity in the MCI group was scattered across the frontal,parietal,temporal,and occipital lobes,while in the d-AD group,it was concentrated within the precentral and postcentral gyri.Notably,hyperconnectivity involving the prefrontal and occipital lobes in the MCI group showed significant declines in the d-AD group.The interhemispheric homologous FC in the d-AD group reduced more significantly than the MCI group.Additionally,in the d-AD group,2 interhemispheric FC within the prefrontal lobe(between the bilateral orbital parts of the inferior frontal gyrus,and between the left medial frontal gyrus and the right middle frontal gyrus)were correlated with MoCA-B scores,and 2 FC(between the bilateral middle occipital gyri,and between the left inferior parietal lobule and the right middle frontal gyrus)were correlated with ADL scores.Conclusion MCI and d-AD exhibit distinct patterns of interhemispheric FC alterations,and the interhemispheric FC changes in AD patients are non-progressive.The close relationships between interhemispheric homologous/non-homologous FC and MoCA-B/ADL scores in d-AD patients provide an objective basis and reference for clinical neuromodulation.

Objective To investigate alterations in interhemispheric functional connectivity(FC)in the cerebral cortices connected via the corpus callosum in patients with Alzheimer's disease(AD),and to explore their relationships with cognitive function and activities of daily living.Methods Resting-state functional magnetic resonance imaging data were collected from 28 patients with Alzheimer's dementia(d-AD),47 patients with mild cognitive impairment(MCI),and 37 healthy controls(HC).Using a trancallosal tract template,32 pairs of homologous cortical brain regions directly connected to 32 subregions of the corpus callosum were selected as regions of interest for interhemispheric FC analysis.Further correlation analyses were performed between FC values in patient groups and their scores on the Montreal Cognitive Assessment-Basic(MoCA-B)Scale and the Activities of Daily Living(ADL)Scale.Results Compared with HC group,both MCI and d-AD groups exhibited hyperconnectivity(significantly increased FC)in interhemispheric non-homologous brain regions.Specifically,hyperconnectivity in the MCI group was scattered across the frontal,parietal,temporal,and occipital lobes,while in the d-AD group,it was concentrated within the precentral and postcentral gyri.Notably,hyperconnectivity involving the prefrontal and occipital lobes in the MCI group showed significant declines in the d-AD group.The interhemispheric homologous FC in the d-AD group reduced more significantly than the MCI group.Additionally,in the d-AD group,2 interhemispheric FC within the prefrontal lobe(between the bilateral orbital parts of the inferior frontal gyrus,and between the left medial frontal gyrus and the right middle frontal gyrus)were correlated with MoCA-B scores,and 2 FC(between the bilateral middle occipital gyri,and between the left inferior parietal lobule and the right middle frontal gyrus)were correlated with ADL scores.Conclusion MCI and d-AD exhibit distinct patterns of interhemispheric FC alterations,and the interhemispheric FC changes in AD patients are non-progressive.The close relationships between interhemispheric homologous/non-homologous FC and MoCA-B/ADL scores in d-AD patients provide an objective basis and reference for clinical neuromodulation.

OBJECTIVE: To investigate the biomechanical characteristics of Schatzker type Ⅱ tibial plateau fracture fixed by different bone grafting methods and internal fixations. METHODS: Twenty-four embalmed specimens of adult knee joint were selected to make Schatzker type Ⅱ tibial plateau fracture models, which were randomly divided into 8 groups (groups A1-D1 and groups A2-D2, n=3). After all the fracture models were restored, non-structural iliac crest bone grafts were implanted in group A1-D1, and structural iliac crest bone grafts in groups A2-D2. Following bone grafting, group A was fixed with a lateral golf locking plate, group B was fixed with lateral golf locking plate combined compression bolt, group C was fixed with lateral tibial "L"-shaped locking plate, and group D was fixed with lateral tibial "L"-shaped locking plate combined compression bolt. Compression and cyclic loading tests were performed on a biomechanical testing machine. A distal femur specimen or a 4-cm-diameter homemade bone cement ball were used as a pressure application mould for each group of models. The specimens were loaded with local compression at a rate of 10 N/s and the mechanical loads were recorded when the vertical displacement of the split bone block reached 2 mm. Then, compressive and cyclic loading tests were conducted on the fixed models of each group. The specimens were compression loaded to 100, 400, 700, and 1 000 N at a speed of 10 N/s to record the vertical displacement of the split bone block. The specimens were also subjected to cyclic loading at 5 Hz and 10 N/s within the ranges 100-300, 100-500, 100-700, and 100-1 000 N to record the vertical displacement of the split bone block at the end of the entire cyclic loading test. The specimens were subjected to cyclic loading tests and the vertical displacement of the split bone block was recorded at the end of the test. RESULTS: When the vertical displacement of the collapsed bone block reached 2 mm, the mechanical load of groups A2-D2 was significantly greater than that of groups A1-D1 ( P<0.05). The mechanical load of groups B and D was significantly greater than that of group A under the two bone grafting methods ( P<0.05); the local mechanical load of group D was significantly greater than that of groups B and C under the structural iliac crest bone grafts ( P<0.05). There was no significant difference ( P>0.05) in the vertical displacement of the split bone blocks between the two bone graft methods when the compressive load was 100, 400, 700 N and the cyclic load was 100-300, 100-500, 100-700 N in groups A-D. However, the vertical displacement of bone block in groups A1-D1 was significantly greater than that in groups A2-D2 ( P<0.05) when the compressive loading was 1 000 N and the cyclic load was 100-1 000 N. The vertical displacement of bone block in group B was significantly smaller than that in group A, and that in group D was significantly smaller than that in group C under the same way of bone graft ( P<0.05). CONCLUSION Compared with non-structural iliac crest bone grafts implantation, structural iliac crest bone grafts is more effective in preventing secondary collapse of Schatzker type Ⅱ tibial plateau fracture, and locking plate combined with compression bolt fixation can provide better articular surface support and resistance to axial compression, and the lateral tibial "L"-shaped locking plate can better highlight its advantages of "raft" fixation and show better mechanical stability.
Humans ; Bone Transplantation/methods* ; Tibial Fractures/physiopathology* ; Fracture Fixation, Internal/instrumentation* ; Biomechanical Phenomena ; Bone Plates ; Ilium/transplantation* ; Adult ; Tibia/surgery* ; Bone Cements ; Knee Joint/surgery* ; Male ; Tibial Plateau Fractures

Clinical management of atopic dermatitis (AD) is challenged by its susceptibility to recurrence, side effects, and high costs. We found that Portulaca oleracea L.-derived nanovesicles (PDNV) exert anti-inflammatory effects by modulating macrophage M1/M2 polarization. These effects were achieved through pathways including inhibition of nuclear factor-κB (NF-κB) and stimulator of interferon genes (STING) protein expression in diseased tissues, demonstrating their potential to ameliorate AD symptoms. To increase the transdermal permeation of PDNV, dissolvable microneedles composed primarily of hyaluronic acid (HA) were developed as an adjunctive means of delivery. Meanwhile, polysaccharides of Portulaca oleracea L., which were synergistic with PDNV, were used as microneedle constituent materials to enhance the mechanical properties and physical stability of HA. This new means of delivery significantly improves the treatment of AD and also provides new options for the efficient utilization of plant extracellular vesicles and the treatment of AD. In addition, transcriptomic analysis of PDNV showed that the mRNAs of Portulaca oleracea L. are closest to those of ferns, which may shed light on related evolutionary and plant species identification studies.

Bio-mineralization has emerged as a promising strategy to enhance vaccine immunogenicity. This study optimized the calcium phosphate (CaP) mineralization process of foot-and-mouth disease virus-like particles (FMD VLPs) to achieve high mineralization efficiency and scalability. Key parameters, including concentrations of Ca²⁺, HPO₄^2-, NaCl, and VLPs, as well as stirring speed, were systematically optimized. Stability of the scaled-up reaction system and immunogenicity of the mineralized vaccine were evaluated. Optimal conditions [25.50 mmol/L Ca(NO₃)₂, 15 mmol/L Na₂HPO₄, 300 mmol/L NaCl, 0.75 mg/mL VLPs, and 1 500 r/min] yielded CaP-mineralized VLPs (VLPs-CaP) with high mineralization efficiency, uniform morphology, and a favorable particle size. Scaling up the reaction by 25 folds maintained consistent mineralization efficiency and particle characteristics. Immunization in mice demonstrated that VLPs-CaP induced higher titers of specific antibodies and neutralizing antibodies than unmineralized VLPs (P < 0.05). Higher IgG2a/IgG1 ratio and enhanced IFN-γ secretion (P < 0.05) further indicated robust cellular immune responses. We establish a stable and scalable protocol for VLPs-CaP, providing a theoretical and technical foundation for developing high-efficacy VLPs-CaP vaccines.
Vaccines, Virus-Like Particle/immunology* ; Immunogenicity, Vaccine ; Calcium Phosphates/chemistry* ; Foot-and-Mouth Disease Virus ; Biomineralization ; Particle Size ; Animals ; Mice ; Antibodies, Neutralizing/blood* ; Antibodies, Viral/blood* ; Immunity, Cellular

Vaccination is a crucial strategy for the prevention and control of infectious diseases. Virus-like particles (VLPs), composed of structural proteins, have garnered significant attention as a novel type of vaccine due to their excellent safety and immunogenicity. However, similar to most vaccine antigens, VLPs exhibit insufficient thermal stability, which not only restricts the widespread application of vaccines but also increases the risk of vaccine inactivation. This study aims to enhance the stability and shelf life of VLPs derived from type A foot-and-mouth disease virus (FMDV) by employing vacuum freeze-drying technology. The optimal lyoprotectant formulation was determined through single-factor and combinatorial screening. Subsequently, the correlation between the immunogenicity of the freeze-dried vaccine and the content of FMDV VLPs was evaluated via a mouse model. The stability of FMDV VLPs before and after freeze-drying was further assessed by storing them at 4, 25, and 37 ℃ for varying time periods. Results indicated that the lyoprotectant formulation No.1, composed of 7.5% trehalose, 0.1% Tween 80, 50 mmol/L glycine, 1% sodium glutamate, and 3% polyvinylpyrrolidone (PVP), effectively preserved the content of FMDV VLPs during the vacuum freeze-drying process. The immunization trial in mice revealed that the levels of specific antibodies, immunoglobulin G1 (IgG1), interleukin-4 (IL-4), and neutralizing antibodies induced by freeze-dried FMDV VLPs were comparable to those induced by non-freeze-dried FMDV VLPs. The heat treatment results showed that the storage periods of freeze-dried FMDV VLPs at 4, 25, and 37 ℃ were significantly longer than those of non-freeze-dried FMDV VLPs. In conclusion, the selected lyoprotectant formulation effectively improved the stability of FMDV VLPs vaccines. This study provides valuable insights for enhancing the stability of novel subunit vaccines.
Freeze Drying/methods* ; Animals ; Foot-and-Mouth Disease Virus/immunology* ; Mice ; Vaccines, Virus-Like Particle/chemistry* ; Foot-and-Mouth Disease/immunology* ; Vacuum ; Drug Stability ; Mice, Inbred BALB C ; Viral Vaccines/immunology*

Objective To explore function-structure covariant patterns in Alzheimer's disease(AD)and mild cognitive impairment(MCI),and to investigate their associations with cognitive function and activities of daily living.Methods three-way parallel group independent component analysis(three-way pGICA),was used to identify the covariant patterns of resting-state functional MRI temporal data,gray matter density maps,and fractional anisotropy(FA)maps,and the differences between different groups were compared.Furthermore,the associations of covariant patterns with the Montreal Cognitive Assessment-Basic(MoCA_B)Scale scores and Activities of Daily Living Scale scores were analyzed.Results The function-structure covariant patterns in AD and MCI were characterized by the enhanced negative functional connectivity between the left posterior salience network and the right default mode network,the decreased gray matter density in the bilateral dorsolateral prefrontal cortex,and the reduced FA values in the left superior corona radiata(correlations:P<0.001,FDR corrected).Compared with HC group,AD group showed significant abnormalities in all identified covariant patterns(P<0.01,FDR corrected),but MCI group only exhibited a significant decrease in gray matter density in the bilateral dorsolateral prefrontal cortex(P<0.05,FDR corrected).Additionally,AD group had significantly lower FA value in the left superior corona radiata than MCI group(P<0.05,FDR corrected).The loadings reflecting the degree of covariation were significantly correlated with the Activities of Daily Living Scale scores(P<0.05,FDR corrected)but not with MoCA_B Scale scores.Conclusion The function-structure covariant patterns in AD and MCI are consistent with the declines in activities of daily living.The multimodal fusion analysis(three-way pGICA)provides a novel approach to understand the brain damage mechanisms underlying the covariant evolution of MCI and AD.

Objective:To analyze the epidemiological characteristics of hospitalized patients diagnosed with sepsis in a large class Ⅲ general hospital in Southwest China in a period of 2 years, and to explore the risk factors related to death in patients with sepsis.Methods:A retrospective study was conducted to select patients with sepsis admitted to Sichuan Provincial People's Hospital from September 1, 2021 to August 31, 2023, and general characteristics such as gender, age, discharge diagnosis, discharge department, hospitalization cost, length of stay, and prognosis during hospitalization were collected. The baseline of two groups of patients were compared, and the risk factors of in-hospital cause of death in patients with sepsis were analyzed by multivariate Logistic regression.Results:A total of 3 568 patients with sepsis were included with median age of 58 (35, 74) years old. Of all patients, there were 2 147 males (60.17%). The median length of hospitalization was 13 (8, 24) days, and the median hospitalization cost was 3.98 (1.87, 8.83) ten thousand yuan. The departments with more than 100 cases of sepsis in 2 years were central intensive care unit (ICU), pediatrics department, nephrology department, emergency medicine department, emergency intensive care unit (EICU), infectious department, respiratory medicine department, hematology department, neonatal care unit and emergency surgical department. A total of 1 210 patients (33.91%) admitted to ICU (including central ICU and EICU). The hospitalization cost of ICU patients were higher [6.7 (3.1, 15.5) ten thousand yuan], the hospitalization duration was longer [9 (3, 17) days], and the mortality was higher [35.29% (427/1 210)]. Among 3 568 patients with sepsis, 448 died and 3 120 survived during hospitalization. The age, male proportion and hospitalization cost of patients with sepsis in the death group were significantly higher than those in the survival group [age (years old): 75 (60, 86) vs. 57 (30, 71), male proportion: 67.86% (304/448) vs. 59.07% (1 843/3 120), hospitalization cost (ten thousand yuan): 6.7 (3.0, 16.9) vs. 3.7 (1.8, 8.1)], the ratio of diabetes mellitus was significantly lower than that of survival group [4.91% (22/448) vs. 10.45% (326/3 120)], the length of hospitalization was shorter than that of survival group [days: 10.0 (3.0, 19.0) vs. 13.0 (8.0, 24.0)], the differences were statistically significant (all P < 0.01). Multivariate Logistic regression analysis showed that male [odds ratio ( OR) = 0.75, 95% confidence interval (95% CI) was 0.59-0.96], elder ( OR = 1.04, 95% CI was 1.03-1.05) and diabetes ( OR = 0.32, 95% CI was 0.19-0.54) were independent risk factors for in-hospital death in patients with sepsis (all P < 0.05). Conclusions:Sepsis is a heavy burden in Southwest China, especially for ICU, with high mortality, high hospitalization costs, and heavy economic burden on patients and society. Male, elder and diabetes were independent risk factors for in-hospital death of sepsis patients.